phase ii study of velcade, decadron, and doxil followed by cyclophosphamide in multiple myeloma

Conditions: Multiple Myeloma

Summary: primary study objectives * to evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without doxil, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients: 1. patients post first line therapy 2. patients with relapsed/refractory disease who are bortezomib-naïve * to evaluate the safety of the combination of bortezomib and dexamethasone, with and without doxil, followed by high-dose cyclophosphamide as therapy for patients with multiple myeloma. secondary study objectives * to evaluate the role of the combination of bortezomib dexamethasone, with and without doxil, followed by high-dose cyclophosphamide on the ability to collect \> 10 x 106 cd34+ cells/kg in \< 7 collections (for both subsets of multiple myeloma patients). * to evaluate the survival of patients who receive the combination of bortezomib dexamethasone, with and without doxil, followed by high-dose cyclophosphamide (for both subsets of patients).


Eligibility criteria:
inclusion criteria: * subject must voluntarily sign and understand written informed consent. * confirmed diagnosis of multiple myeloma as specified by the swog criteria and is detailed in appendix i. * measurable disease as defined the following: 1. for patients post induction therapy, any measurable paraprotein in the serum or urine and/or any plasmacytoma present on physical exam or imaging. 2. for patients with relapsed/refractory disease, \> 0.5 g/dl serum monoclonal protein, \> 0.1 g/dl serum free light chains, \> 0.2 g/24 hrs urinary m-protein excretion, and/or measurable plasmacytoma(s). * age \> or = than 18 years at the time of signing the informed consent form. * karnofsky performance status\> or =70% (\>60% if due to bony involvement of myeloma). * group a (post-induction therapy)- patients who have received only one prior treatment regimen (eg vad, thal/dex, blt-d, mp, bird, or dvd) with at least 20 patients having received a revlimid based regimen or group b(\>1st line of therapy)- patients with relapsed/refractory multiple myeloma who have received two or more prior treatment regimens . * if the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study and must use effective contraception throughout the course of the study. * life expectancy \> 12 weeks. * absolute neutrophil count (anc)\> or = 1500 cells/mm3 (\> or = 1000 for patients with bone marrow biopsy displaying \> 50% involvement by myeloma) * platelets count \> or = 50,000/mm3 (\> or = 30,000 for patients with bone marrow biopsy displaying \> 50% involvement by myeloma) * hemoglobin \> 9.0 g/dl * serum sgot/ast \<3.0 x upper limits of normal (uln) * serum sgpt/alt \<3.0 x upper limits of normal (uln) * serum creatinine \ 40ml/min * serum total bilirubin \< 1.5 x uln * patients must have a muga scan with lvef \>50% exclusion criteria: * patients with non-secretory mm (no measurable monoclonal protein, free light chains, and/or m-spike in blood or urine) unless measurable disease is available with imaging techniques such as mri and pet scan. * prior treatment with bortezomib. * peripheral neuropathy of \> grade 2 as defined by ctcae version 3.0 (see appendix ii) * history of allergic reactions to compounds containing mannitol, bortezomib, conventional formulation of doxorubicin hcl or the components of doxil. * prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years. * nyha class iii or iv heart disease. history of active unstable angina, congestive heart disease, serious uncontrolled cardiac arrhythmia or myocardial infarction within 6 months. * female patients who are pregnant or breastfeeding. women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. * known hiv or hepatitis a, b, or c positivity * active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program. * any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis). * no prior anti-myeloma therapy within 2 weeks of treatment initiation.